Anastrozole: Difference between revisions

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{{drugbox
{{DrugProjectFormSinglePage
| IUPAC_name = 2-[3-(1-cyano-1-methyl-ethyl)- 5-(1''H''-1,2,4-triazol-1-ylmethyl)phenyl]- 2-methyl- propanenitrile
|authorTag=
| image =
 
| CAS_number = 120511-73-1
{{VP}}
| ATC_prefix = L02
 
| ATC_suffix = BG03
<!--Overview-->
| ATC_supplemental =  
 
| PubChem = 2187
|genericName=
| DrugBank = APRD00016
 
| C = 17 | H = 19 | N = 5
Anastrozole
| molecular_weight = 293.366 g/mol
 
| bioavailability = 83-85%
|aOrAn=
| protein_bound = 40%
 
| metabolism = 85% hepatic
an
| excretion = 11% renal
 
| elimination_half-life = 72 hours
|drugClass=
| pregnancy_us = D
 
| pregnancy_category =  
aromatase inhibitor
| legal_status = Rx only (U.S.)
 
| routes_of_administration = oral
|indication=
}}
 
{{SI}}
adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer, postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer, advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy
 
|hasBlackBoxWarning=
 
|adverseReactions=
 
[[hot flashes]], [[asthenia]], [[arthritis]], [[pain]], [[arthralgia]], [[pharyngitis]], [[hypertension]], [[depression]], [[nausea]] and [[vomiting]], [[rash]], [[osteoporosis]], [[fractures]], [[back pain]], [[insomnia]], [[headache]], [[peripheral edema]] and [[lymphedema]]
 
<!--Black Box Warning-->
 
|blackBoxWarningTitle=
Title
 
|blackBoxWarningBody=
<i><span style="color:#FF0000;">ConditionName: </span></i>
 
* Content
 
<!--Adult Indications and Dosage-->
 
<!--FDA-Labeled Indications and Dosage (Adult)-->
 
|fdaLIADAdult=
 
=====Adjuvant Treatment=====
 
*Anastrozole tablets are indicated for adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer.
 
=====First-Line Treatment=====
 
*Anastrozole tablets are indicated for the first-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer.
 
=====Second-Line Treatment=====
 
*Anastrozole tablets are indicated for the treatment of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy. Patients with ER-negative disease and patients who did not respond to previous tamoxifen therapy rarely responded to anastrozole tablets.
 
*Recommended Dose
:*The dose of anastrozole tablet is one 1 mg tablet taken once a day. For patients with advanced breast cancer, anastrozole tablets should be continued until tumor progression. Anastrozole tablets can be taken with or without food.
:*For adjuvant treatment of early breast cancer in postmenopausal women, the optimal duration of therapy is unknown. In the ATAC trial, anastrozole was administered for five years.
:*No dosage adjustment is necessary for patients with renal impairment or for elderly patients.
 
*Patients with Hepatic Impairment
:*No changes in dose are recommended for patients with mild-to-moderate hepatic impairment. Anastrozole has not been studied in patients with severe hepatic impairment [see Use in Specific Populations (8.7)].
 
<!--Off-Label Use and Dosage (Adult)-->
 
<!--Guideline-Supported Use (Adult)-->
 
|offLabelAdultGuideSupport=
 
=====Condition1=====
 
* Developed by:
 
* Class of Recommendation:
 
* Strength of Evidence:
 
* Dosing Information
 
:* Dosage
 
=====Condition2=====
 
There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
 
<!--Non–Guideline-Supported Use (Adult)-->
 
|offLabelAdultNoGuideSupport=
 
=====Condition1=====
 
* Dosing Information
 
:* Dosage
 
=====Condition2=====
 
There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
 
<!--Pediatric Indications and Dosage-->
 
<!--FDA-Labeled Indications and Dosage (Pediatric)-->
 
|fdaLIADPed=
 
=====Condition1=====
 
* Dosing Information
 
:* Dosage
 
=====Condition2=====
 
There is limited information regarding <i>FDA-Labeled Use</i> of {{PAGENAME}} in pediatric patients.
 
<!--Off-Label Use and Dosage (Pediatric)-->
 
<!--Guideline-Supported Use (Pediatric)-->
 
|offLabelPedGuideSupport=
 
=====Condition1=====
 
* Developed by:
 
* Class of Recommendation:
 
* Strength of Evidence:
 
* Dosing Information
 
:* Dosage
 
=====Condition2=====
 
There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
 
<!--Non–Guideline-Supported Use (Pediatric)-->
 
|offLabelPedNoGuideSupport=
 
=====Condition1=====
 
* Dosing Information
 
:* Dosage
 
=====Condition2=====
 
There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
 
<!--Contraindications-->
 
|contraindications=
 
=====Pregnancy and Premenopausal Women=====
 
*Anastrozole may cause fetal harm when administered to a pregnant woman and offers no clinical benefit to premenopausal women with breast cancer. Anastrozole is contraindicated in women who are or may become pregnant. There are no adequate and well-controlled studies in pregnant women using anastrozole. If anastrozole is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus or potential risk for loss of the pregnancy [see Use in Specific Populations (8.1)].
 
=====Hypersensitivity=====
 
*Anastrozole is contraindicated in any patient who has shown a hypersensitivity reaction to the drug or to any of the excipients. Observed reactions include anaphylaxis, angioedema, and urticaria [see Adverse Reactions (6.2)].
 
<!--Warnings-->
 
|warnings=
 
====Precautions====
 
*Ischemic Cardiovascular Events
:*In women with pre-existing ischemic heart disease, an increased incidence of ischemic cardiovascular events was observed with anastrozole in the ATAC trial (17% of patients on anastrozole and 10% of patients on tamoxifen). Consider risk and benefits of anastrozole therapy in patients with pre-existing ischemic heart disease [see Adverse Reactions (6.1)].
 
 
*Bone Effects
:*Results from the ATAC trial bone substudy at 12 and 24 months demonstrated that patients receiving anastrozole had a mean decrease in both lumbar spine and total hip bone mineral density (BMD) compared to baseline. Patients receiving tamoxifen had a mean increase in both lumbar spine and total hip BMD compared to baseline. Consider bone mineral density monitoring in patients treated with anastrozole [see Adverse Reactions (6.1)].
 
 
*Cholesterol
:*During the ATAC trial, more patients receiving anastrozole were reported to have elevated serum cholesterol compared to patients receiving tamoxifen (9% versus 3.5%, respectively) [see Adverse Reactions (6.1)].
 
<!--Adverse Reactions-->
 
<!--Clinical Trials Experience-->
 
|clinicalTrials=
 
 
*Serious adverse reactions with anastrozole occurring in less than 1 in 10,000 patients, are: 1) skin reactions such as lesions, ulcers, or blisters; 2) allergic reactions with swelling of the face, lips, tongue, and/or throat. This may cause difficulty in swallowing and/or breathing; and 3) changes in blood tests of the liver function, including inflammation of the liver with symptoms that may include a general feeling of not being well, with or without jaundice, liver pain or liver swelling [see Adverse Reactions (6.2)].
 
*Common adverse reactions (occurring with an incidence of ≥10%) in women taking anastrozole included: hot flashes, asthenia, arthritis, pain, arthralgia, pharyngitis, hypertension, depression, nausea and vomiting, rash, osteoporosis, fractures, back pain, insomnia, pain, headache, bone pain, peripheral edema, increased cough, dyspnea, pharyngitis and lymphedema.
 
*In the ATAC trial, the most common reported adverse reaction (>0.1%) leading to discontinuation of therapy for both treatment groups was hot flashes, although there were fewer patients who discontinued therapy as a result of hot flashes in the anastrozole group.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
 
 
*Adjuvant Therapy
:*Adverse reaction data for adjuvant therapy are based on the ATAC trial [see Clinical Studies (14.1)]. The median duration of adjuvant treatment for safety evaluation was 59.8 months and 59.6 months for patients receiving anastrozole 1 mg and tamoxifen 20 mg, respectively.
Adverse reactions occurring with an incidence of at least 5% in either treatment group during treatment or within 14 days of the end of treatment are presented in Table 1.
 
 
 
 
Certain adverse reactions and combinations of adverse reactions were prospectively specified for analysis, based on the known pharmacologic properties and side effect profiles of the two drugs (see Table 2).
 
 
 
Ischemic Cardiovascular Events
Between treatment arms in the overall population of 6186 patients, there was no statistical difference in ischemic cardiovascular events (4% anastrozole vs. 3% tamoxifen). In the overall population, angina pectoris was reported in 71/3092 (2.3%) patients in the anastrozole arm and 51/3094 (1.6%) patients in the tamoxifen arm; myocardial infarction was reported in 37/3092 (1.2%) patients in the anastrozole arm and 34/3094 (1.1%) patients in the tamoxifen arm.
In women with pre-existing ischemic heart disease 465/6186 (7.5%), the incidence of ischemic cardiovascular events was 17% in patients on anastrozole and 10% in patients on tamoxifen. In this patient population, angina pectoris was reported in 25/216 (11.6%) patients receiving anastrozole and 13/249 (5.2%) patients receiving tamoxifen; myocardial infarction was reported in 2/216 (0.9%) patients receiving anastrozole and 8/249 (3.2%) patients receiving tamoxifen.
Bone Mineral Density Findings
Results from the ATAC trial bone substudy at 12 and 24 months demonstrated that patients receiving anastrozole had a mean decrease in both lumbar spine and total hip bone mineral density (BMD) compared to baseline. Patients receiving tamoxifen had a mean increase in both lumbar spine and total hip BMD compared to baseline.
Because anastrozole lowers circulating estrogen levels it may cause a reduction in bone mineral density.
A post-marketing trial assessed the combined effects of anastrozole and the bisphosphonate risedronate on changes from baseline in BMD and markers of bone resorption and formation in postmenopausal women with hormone receptor-positive early breast cancer. All patients received calcium and vitamin D supplementation. At 12 months, small reductions in lumbar spine bone mineral density were noted in patients not receiving bisphosphonates. Bisphosphonate treatment preserved bone density in most patients at risk of fracture.
Postmenopausal women with early breast cancer scheduled to be treated with anastrozole should have their bone status managed according to treatment guidelines already available for postmenopausal women at similar risk of fragility fracture.
Cholesterol
During the ATAC trial, more patients receiving anastrozole were reported to have an elevated serum cholesterol compared to patients receiving tamoxifen (9% versus 3.5%, respectively).
A post-marketing trial also evaluated any potential effects of anastrozole on lipid profile. In the primary analysis population for lipids (anastrozole alone), there was no clinically significant change in LDL-C from baseline to 12 months and HDL-C from baseline to 12 months.
In secondary population for lipids (anastrozole+risedronate), there also was no clinically significant change in LDL-C and HDL-C from baseline to 12 months.
In both populations for lipids, there was no clinically significant difference in total cholesterol (TC) or serum triglycerides (TG) at 12 months compared with baseline.
In this trial, treatment for 12 months with anastrozole alone had a neutral effect on lipid profile. Combination treatment with anastrozole and risedronate also had a neutral effect on lipid profile.
The trial provides evidence that postmenopausal women with early breast cancer scheduled to be treated with anastrozole should be managed using the current National Cholesterol Education Program guidelines for cardiovascular risk-based management of individual patients with LDL elevations.
Other Adverse Reactions
Patients receiving anastrozole had an increase in joint disorders (including arthritis, arthrosis and arthralgia) compared with patients receiving tamoxifen. Patients receiving anastrozole had an increase in the incidence of all fractures (specifically fractures of spine, hip and wrist) [315 (10%)] compared with patients receiving tamoxifen [209 (7%)].
Patients receiving anastrozole had a higher incidence of carpal tunnel syndrome [78 (2.5%)] compared with patients receiving tamoxifen [22 (0.7%)].
Vaginal bleeding occurred more frequently in the tamoxifen-treated patients versus the anastrozole -treated patients 317 (10%) versus 167 (5%), respectively.
Patients receiving anastrozole had a lower incidence of hot flashes, vaginal bleeding, vaginal discharge, endometrial cancer, venous thromboembolic events and ischemic cerebrovascular events compared with patients receiving tamoxifen.
10-year median follow-up Safety Results from the ATAC Trial
Results are consistent with the previous analyses.
Serious adverse reactions were similar between anastrozole (50%) and tamoxifen (51%).
Cardiovascular events were consistent with the known safety profiles of anastrozole and tamoxifen.
The cumulative incidences of all first fractures (both serious and non-serious, occurring either during or after treatment) was higher in the anastrozole group (15%) compared to the tamoxifen group (11%). This increased first fracture rate during treatment did not continue in the post-treatment follow-up period.
The cumulative incidence of new primary cancers was similar in the anastrozole group (13.7%) compared to the tamoxifen group (13.9%). Consistent with the previous analyses, endometrial cancer was higher in the tamoxifen group (0.8%) compared to the anastrozole group (0.2%).
The overall number of deaths (during or off-trial treatment) was similar between the treatment groups. There were more deaths related to breast cancer in the tamoxifen than in the anastrozole treatment group.
First-Line Therapy
Adverse reactions occurring with an incidence of at least 5% in either treatment group of trials 0030 and 0027 during or within 2 weeks of the end of treatment are shown in Table 3.
 
<!--Postmarketing Experience-->
 
|postmarketing=
 
There is limited information regarding <i>Postmarketing Experience</i> of {{PAGENAME}} in the drug label.
 
=====Body as a Whole=====
 
 
 
=====Cardiovascular=====
 
 
 
=====Digestive=====
 
 
 
=====Endocrine=====
 
 
 
=====Hematologic and Lymphatic=====
 
 
 
=====Metabolic and Nutritional=====
 
 
 
=====Musculoskeletal=====
 
 
 
=====Neurologic=====
 
 
 
=====Respiratory=====
 
 
 
=====Skin and Hypersensitivy Reactions=====
 
 
 
=====Special Senses=====
 
 
 
=====Urogenital=====
 
 
 
=====Miscellaneous=====
 
 
 
<!--Drug Interactions-->
 
|drugInteractions=
 
* Drug
:* Description
 
<!--Use in Specific Populations-->
 
|useInPregnancyFDA=
* '''Pregnancy Category'''
 
|useInPregnancyAUS=
* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''
 
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of {{PAGENAME}} in women who are pregnant.
 
|useInLaborDelivery=
There is no FDA guidance on use of {{PAGENAME}} during labor and delivery.
 
|useInNursing=
There is no FDA guidance on the use of {{PAGENAME}} with respect to nursing mothers.
 
|useInPed=
There is no FDA guidance on the use of {{PAGENAME}} with respect to pediatric patients.
 
|useInGeri=
There is no FDA guidance on the use of {{PAGENAME}} with respect to geriatric patients.
 
|useInGender=
There is no FDA guidance on the use of {{PAGENAME}} with respect to specific gender populations.
 
|useInRace=
There is no FDA guidance on the use of {{PAGENAME}} with respect to specific racial populations.
 
|useInRenalImpair=
There is no FDA guidance on the use of {{PAGENAME}} in patients with renal impairment.
 
|useInHepaticImpair=
There is no FDA guidance on the use of {{PAGENAME}} in patients with hepatic impairment.
 
|useInReproPotential=
There is no FDA guidance on the use of {{PAGENAME}} in women of reproductive potentials and males.
 
|useInImmunocomp=
There is no FDA guidance one the use of {{PAGENAME}} in patients who are immunocompromised.
 
<!--Administration and Monitoring-->
 
|administration=
 
* Oral
 
* Intravenous
 
|monitoring=
 
There is limited information regarding <i>Monitoring</i> of {{PAGENAME}} in the drug label.
 
* Description
 
<!--IV Compatibility-->
 
|IVCompat=
 
There is limited information regarding <i>IV Compatibility</i> of {{PAGENAME}} in the drug label.
 
<!--Overdosage-->
 
|overdose=
 
===Acute Overdose===
 
====Signs and Symptoms====
 
* Description
 
====Management====
 
* Description
 
===Chronic Overdose===
 
There is limited information regarding <i>Chronic Overdose</i> of {{PAGENAME}} in the drug label.
 
<!--Pharmacology-->
 
<!--Drug box 2-->
 
|drugBox=
 
 
 
<!--Mechanism of Action-->
 
|mechAction=
 
*
 
<!--Structure-->
 
|structure=
 
*
 
: [[File:{{PAGENAME}}01.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
 
<!--Pharmacodynamics-->
 
|PD=
 
There is limited information regarding <i>Pharmacodynamics</i> of {{PAGENAME}} in the drug label.
 
<!--Pharmacokinetics-->
 
|PK=
 
There is limited information regarding <i>Pharmacokinetics</i> of {{PAGENAME}} in the drug label.
 
<!--Nonclinical Toxicology-->
 
|nonClinToxic=
 
There is limited information regarding <i>Nonclinical Toxicology</i> of {{PAGENAME}} in the drug label.
 
<!--Clinical Studies-->
 
|clinicalStudies=
 
There is limited information regarding <i>Clinical Studies</i> of {{PAGENAME}} in the drug label.
 
<!--How Supplied-->
 
|howSupplied=
 
*
 
<!--Patient Counseling Information-->
 
|fdaPatientInfo=
 
There is limited information regarding <i>Patient Counseling Information</i> of {{PAGENAME}} in the drug label.
 
<!--Precautions with Alcohol-->
 
|alcohol=
 
* Alcohol-{{PAGENAME}} interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.


<!--Brand Names-->


==Overview==
|brandNames=
'''Anastrozole''' ([[International Nonproprietary Name|INN]], trade name: '''Arimidex®''') is a drug indicated in the treatment of [[breast cancer]] in post-[[menopause|menopausal]] women.  It is used both in [[adjuvant#Oncology|adjuvant]] therapy (i.e. following surgery) and in [[metastasis|metastatic]] breast cancer.  It has the effect of decreasing the amount of [[estrogen]]s that the body makes.


Anastrozole belongs in the class of drugs known as [[aromatase inhibitor]]s. It inhibits the enzyme [[aromatase]], which is responsible for converting [[androgen]]s (produced by women in the [[adrenal gland]]s) to estrogens.
* ®<ref>{{Cite web | title = | url =  }}</ref>


The ATAC (Arimidex, [[Tamoxifen]], Alone or in Combination) trial represents a long-term follow-up study of 9366 women with localized [[breast cancer]] who received either anastrozole, tamoxifen, or both.<ref>{{cite journal |author=Howell A, Cuzick J, Baum M, ''et al'' |title=Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer |journal=[[The_Lancet|Lancet]] |volume=365 |issue=9453 |pages=60-2 |year=2005 |pmid=15639680 |doi=10.1016/S0140-6736(04)17666-6}}</ref> After more than 5 years the group that received anastrozole had significantly better clinical results than the tamoxifen group. The trial suggested that anastrozole is the preferred medical therapy for postmenopausal women with localized breast cancer that is [[estrogen receptor]] positive.
<!--Look-Alike Drug Names-->


==Usage for men==
|lookAlike=
While officially indicated for women, this drug has proven effective in the off-label use of reducing estrogens (in particular and more importantly, estradiol) in men.  Excess estradiol in men can cause [[benign prostatic hyperplasia]], [[gynecomastia]], and symptoms of [[hypogonadism]].  Some athletes and [[Bodybuilding|body builders]] will also use anastrozole as a part of their [[steroid cycle]] to reduce and prevent symptoms of excess estrogens; in particular, [[gynecomastia]] and water retention.


Study data currently suggests that dosages of 0.5mg to 1mg a day reduce serum estradiol by about 50% in men, which differs from the typical reduction in postmenopausal women.  However the reduction may be different for men with grossly elevated estradiol (clinical data is currently lacking).
* A® — B®<ref name="www.ismp.org">{{Cite web | last =  | first =  | title = http://www.ismp.org | url = http://www.ismp.org | publisher =  | date =  }}</ref>


==Usage for children==
<!--Drug Shortage Status-->
This drug is frequently used in the treatment of growth disorder affected children to stop or slow the onset of puberty. The treatment of the growth disorder is through hormones which may trigger the early onset of puberty (precocious puberty). At the onset of puberty the bone growth plates begin to close. This can occur in children as young as 5 years old so for children severely behind in growth, the opportunity for increased growth is diminished. Arimidex is shown to slow or stop this process.


===Pill Images===
|drugShortage=
{{TempDrugImages}}
}}
{{PillImage|fileName=Anastrozole_NDC_03786034.jpg|drugName=Anastrozole|NDC=03786034|drugAuthor=Mylan Pharmaceuticals Inc.|ingredients=ANASTROZOLE[ANASTROZOLE]|pillImprint=M;34|dosageValue=1|dosageUnit=mg|pillColor=White|pillShape=Round|pillSize=6|pillScore=1}}
{{PillImage|fileName=ARIMIDEX_NDC_03100201.jpg|drugName=ARIMIDEX|NDC=03100201|drugAuthor=AstraZeneca Pharmaceuticals LP|ingredients=ANASTROZOLE[ANASTROZOLE]|pillImprint=adx1|dosageValue=1|dosageUnit=mg|pillColor=White|pillShape=Round|pillSize=6|pillScore=1}}
{{PillImage|fileName=Anastrozole_NDC_604290286.jpg|drugName=Anastrozole|NDC=604290286|drugAuthor=Golden State Medical Supply, Inc.|ingredients=ANASTROZOLE[ANASTROZOLE]|pillImprint=APO;AN;1|dosageValue=1|dosageUnit=mg|pillColor=White|pillShape=Round|pillSize=6|pillScore=1}}
{{PillImage|fileName=ANASTROZOLE_NDC_627560250.jpg|drugName=ANASTROZOLE|NDC=627560250|drugAuthor=Sun Pharmaceutical Industries Limited |ingredients=ANASTROZOLE[ANASTROZOLE]|pillImprint=A1|dosageValue=1|dosageUnit=mg|pillColor=White|pillShape=Round|pillSize=6|pillScore=1}}
{{PillImage|fileName=Anastrozole_NDC_00937536.jpg|drugName=Anastrozole|NDC=00937536|drugAuthor=Teva Pharmaceuticals USA Inc|ingredients=ANASTROZOLE[ANASTROZOLE]|pillImprint=TEVA;A10|dosageValue=1|dosageUnit=mg|pillColor=White|pillShape=Round|pillSize=6|pillScore=1}}


<!--Pill Image-->


==References==
{{PillImage
<div class="references-small">
|fileName=No image.jpg|This image is provided by the National Library of Medicine.
{{reflist|2}}
|drugName=
</div>
|NDC=
|drugAuthor=
|ingredients=
|pillImprint=
|dosageValue=
|dosageUnit=
|pillColor=
|pillShape=
|pillSize=
|pillScore=
}}


<!--Label Display Image-->


==External links==
{{LabelImage
* [http://www.arimidex.com/ Arimidex.com - Information about Arimidex and breast cancer]
|fileName={{PAGENAME}}11.png|This image is provided by the National Library of Medicine.
{{Sex hormones}}
}}


{{LabelImage
|fileName={{PAGENAME}}11.png|This image is provided by the National Library of Medicine.
}}


[[Category:Aromatase inhibitors]]
<!--Category-->
[[Category:Endocrinology]]


[[it:Anastrozolo]]
[[Category:Drug]]
[[pt:Anastrozole]]
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Revision as of 14:37, 29 August 2014

Anastrozole
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vignesh Ponnusamy, M.B.B.S. [2]

Disclaimer

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Overview

Anastrozole is an aromatase inhibitor that is FDA approved for the {{{indicationType}}} of adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer, postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer, advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy. Common adverse reactions include hot flashes, asthenia, arthritis, pain, arthralgia, pharyngitis, hypertension, depression, nausea and vomiting, rash, osteoporosis, fractures, back pain, insomnia, headache, peripheral edema and lymphedema.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Adjuvant Treatment
  • Anastrozole tablets are indicated for adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer.
First-Line Treatment
  • Anastrozole tablets are indicated for the first-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer.
Second-Line Treatment
  • Anastrozole tablets are indicated for the treatment of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy. Patients with ER-negative disease and patients who did not respond to previous tamoxifen therapy rarely responded to anastrozole tablets.
  • Recommended Dose
  • The dose of anastrozole tablet is one 1 mg tablet taken once a day. For patients with advanced breast cancer, anastrozole tablets should be continued until tumor progression. Anastrozole tablets can be taken with or without food.
  • For adjuvant treatment of early breast cancer in postmenopausal women, the optimal duration of therapy is unknown. In the ATAC trial, anastrozole was administered for five years.
  • No dosage adjustment is necessary for patients with renal impairment or for elderly patients.
  • Patients with Hepatic Impairment
  • No changes in dose are recommended for patients with mild-to-moderate hepatic impairment. Anastrozole has not been studied in patients with severe hepatic impairment [see Use in Specific Populations (8.7)].

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

Condition1
  • Developed by:
  • Class of Recommendation:
  • Strength of Evidence:
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Guideline-Supported Use of Anastrozole in adult patients.

Non–Guideline-Supported Use

Condition1
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Anastrozole in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Condition1
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding FDA-Labeled Use of Anastrozole in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

Condition1
  • Developed by:
  • Class of Recommendation:
  • Strength of Evidence:
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Guideline-Supported Use of Anastrozole in pediatric patients.

Non–Guideline-Supported Use

Condition1
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Anastrozole in pediatric patients.

Contraindications

Pregnancy and Premenopausal Women
  • Anastrozole may cause fetal harm when administered to a pregnant woman and offers no clinical benefit to premenopausal women with breast cancer. Anastrozole is contraindicated in women who are or may become pregnant. There are no adequate and well-controlled studies in pregnant women using anastrozole. If anastrozole is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus or potential risk for loss of the pregnancy [see Use in Specific Populations (8.1)].
Hypersensitivity
  • Anastrozole is contraindicated in any patient who has shown a hypersensitivity reaction to the drug or to any of the excipients. Observed reactions include anaphylaxis, angioedema, and urticaria [see Adverse Reactions (6.2)].

Warnings

Precautions

  • Ischemic Cardiovascular Events
  • In women with pre-existing ischemic heart disease, an increased incidence of ischemic cardiovascular events was observed with anastrozole in the ATAC trial (17% of patients on anastrozole and 10% of patients on tamoxifen). Consider risk and benefits of anastrozole therapy in patients with pre-existing ischemic heart disease [see Adverse Reactions (6.1)].


  • Bone Effects
  • Results from the ATAC trial bone substudy at 12 and 24 months demonstrated that patients receiving anastrozole had a mean decrease in both lumbar spine and total hip bone mineral density (BMD) compared to baseline. Patients receiving tamoxifen had a mean increase in both lumbar spine and total hip BMD compared to baseline. Consider bone mineral density monitoring in patients treated with anastrozole [see Adverse Reactions (6.1)].


  • Cholesterol
  • During the ATAC trial, more patients receiving anastrozole were reported to have elevated serum cholesterol compared to patients receiving tamoxifen (9% versus 3.5%, respectively) [see Adverse Reactions (6.1)].

Adverse Reactions

Clinical Trials Experience

  • Serious adverse reactions with anastrozole occurring in less than 1 in 10,000 patients, are: 1) skin reactions such as lesions, ulcers, or blisters; 2) allergic reactions with swelling of the face, lips, tongue, and/or throat. This may cause difficulty in swallowing and/or breathing; and 3) changes in blood tests of the liver function, including inflammation of the liver with symptoms that may include a general feeling of not being well, with or without jaundice, liver pain or liver swelling [see Adverse Reactions (6.2)].
  • Common adverse reactions (occurring with an incidence of ≥10%) in women taking anastrozole included: hot flashes, asthenia, arthritis, pain, arthralgia, pharyngitis, hypertension, depression, nausea and vomiting, rash, osteoporosis, fractures, back pain, insomnia, pain, headache, bone pain, peripheral edema, increased cough, dyspnea, pharyngitis and lymphedema.
  • In the ATAC trial, the most common reported adverse reaction (>0.1%) leading to discontinuation of therapy for both treatment groups was hot flashes, although there were fewer patients who discontinued therapy as a result of hot flashes in the anastrozole group.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.


  • Adjuvant Therapy
  • Adverse reaction data for adjuvant therapy are based on the ATAC trial [see Clinical Studies (14.1)]. The median duration of adjuvant treatment for safety evaluation was 59.8 months and 59.6 months for patients receiving anastrozole 1 mg and tamoxifen 20 mg, respectively.

Adverse reactions occurring with an incidence of at least 5% in either treatment group during treatment or within 14 days of the end of treatment are presented in Table 1.



Certain adverse reactions and combinations of adverse reactions were prospectively specified for analysis, based on the known pharmacologic properties and side effect profiles of the two drugs (see Table 2).


Ischemic Cardiovascular Events Between treatment arms in the overall population of 6186 patients, there was no statistical difference in ischemic cardiovascular events (4% anastrozole vs. 3% tamoxifen). In the overall population, angina pectoris was reported in 71/3092 (2.3%) patients in the anastrozole arm and 51/3094 (1.6%) patients in the tamoxifen arm; myocardial infarction was reported in 37/3092 (1.2%) patients in the anastrozole arm and 34/3094 (1.1%) patients in the tamoxifen arm. In women with pre-existing ischemic heart disease 465/6186 (7.5%), the incidence of ischemic cardiovascular events was 17% in patients on anastrozole and 10% in patients on tamoxifen. In this patient population, angina pectoris was reported in 25/216 (11.6%) patients receiving anastrozole and 13/249 (5.2%) patients receiving tamoxifen; myocardial infarction was reported in 2/216 (0.9%) patients receiving anastrozole and 8/249 (3.2%) patients receiving tamoxifen. Bone Mineral Density Findings Results from the ATAC trial bone substudy at 12 and 24 months demonstrated that patients receiving anastrozole had a mean decrease in both lumbar spine and total hip bone mineral density (BMD) compared to baseline. Patients receiving tamoxifen had a mean increase in both lumbar spine and total hip BMD compared to baseline. Because anastrozole lowers circulating estrogen levels it may cause a reduction in bone mineral density. A post-marketing trial assessed the combined effects of anastrozole and the bisphosphonate risedronate on changes from baseline in BMD and markers of bone resorption and formation in postmenopausal women with hormone receptor-positive early breast cancer. All patients received calcium and vitamin D supplementation. At 12 months, small reductions in lumbar spine bone mineral density were noted in patients not receiving bisphosphonates. Bisphosphonate treatment preserved bone density in most patients at risk of fracture. Postmenopausal women with early breast cancer scheduled to be treated with anastrozole should have their bone status managed according to treatment guidelines already available for postmenopausal women at similar risk of fragility fracture. Cholesterol During the ATAC trial, more patients receiving anastrozole were reported to have an elevated serum cholesterol compared to patients receiving tamoxifen (9% versus 3.5%, respectively). A post-marketing trial also evaluated any potential effects of anastrozole on lipid profile. In the primary analysis population for lipids (anastrozole alone), there was no clinically significant change in LDL-C from baseline to 12 months and HDL-C from baseline to 12 months. In secondary population for lipids (anastrozole+risedronate), there also was no clinically significant change in LDL-C and HDL-C from baseline to 12 months. In both populations for lipids, there was no clinically significant difference in total cholesterol (TC) or serum triglycerides (TG) at 12 months compared with baseline. In this trial, treatment for 12 months with anastrozole alone had a neutral effect on lipid profile. Combination treatment with anastrozole and risedronate also had a neutral effect on lipid profile. The trial provides evidence that postmenopausal women with early breast cancer scheduled to be treated with anastrozole should be managed using the current National Cholesterol Education Program guidelines for cardiovascular risk-based management of individual patients with LDL elevations. Other Adverse Reactions Patients receiving anastrozole had an increase in joint disorders (including arthritis, arthrosis and arthralgia) compared with patients receiving tamoxifen. Patients receiving anastrozole had an increase in the incidence of all fractures (specifically fractures of spine, hip and wrist) [315 (10%)] compared with patients receiving tamoxifen [209 (7%)]. Patients receiving anastrozole had a higher incidence of carpal tunnel syndrome [78 (2.5%)] compared with patients receiving tamoxifen [22 (0.7%)]. Vaginal bleeding occurred more frequently in the tamoxifen-treated patients versus the anastrozole -treated patients 317 (10%) versus 167 (5%), respectively. Patients receiving anastrozole had a lower incidence of hot flashes, vaginal bleeding, vaginal discharge, endometrial cancer, venous thromboembolic events and ischemic cerebrovascular events compared with patients receiving tamoxifen. 10-year median follow-up Safety Results from the ATAC Trial Results are consistent with the previous analyses. Serious adverse reactions were similar between anastrozole (50%) and tamoxifen (51%). Cardiovascular events were consistent with the known safety profiles of anastrozole and tamoxifen. The cumulative incidences of all first fractures (both serious and non-serious, occurring either during or after treatment) was higher in the anastrozole group (15%) compared to the tamoxifen group (11%). This increased first fracture rate during treatment did not continue in the post-treatment follow-up period. The cumulative incidence of new primary cancers was similar in the anastrozole group (13.7%) compared to the tamoxifen group (13.9%). Consistent with the previous analyses, endometrial cancer was higher in the tamoxifen group (0.8%) compared to the anastrozole group (0.2%). The overall number of deaths (during or off-trial treatment) was similar between the treatment groups. There were more deaths related to breast cancer in the tamoxifen than in the anastrozole treatment group. First-Line Therapy Adverse reactions occurring with an incidence of at least 5% in either treatment group of trials 0030 and 0027 during or within 2 weeks of the end of treatment are shown in Table 3.

Postmarketing Experience

There is limited information regarding Postmarketing Experience of Anastrozole in the drug label.

Body as a Whole
Cardiovascular
Digestive
Endocrine
Hematologic and Lymphatic
Metabolic and Nutritional
Musculoskeletal
Neurologic
Respiratory
Skin and Hypersensitivy Reactions
Special Senses
Urogenital
Miscellaneous

Drug Interactions

  • Drug
  • Description

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

  • Pregnancy Category


Pregnancy Category (AUS):

  • Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Anastrozole in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Anastrozole during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Anastrozole with respect to nursing mothers.

Pediatric Use

There is no FDA guidance on the use of Anastrozole with respect to pediatric patients.

Geriatic Use

There is no FDA guidance on the use of Anastrozole with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Anastrozole with respect to specific gender populations.

Race

There is no FDA guidance on the use of Anastrozole with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Anastrozole in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Anastrozole in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Anastrozole in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Anastrozole in patients who are immunocompromised.

Administration and Monitoring

Administration

  • Oral
  • Intravenous

Monitoring

There is limited information regarding Monitoring of Anastrozole in the drug label.

  • Description

IV Compatibility

There is limited information regarding IV Compatibility of Anastrozole in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

  • Description

Management

  • Description

Chronic Overdose

There is limited information regarding Chronic Overdose of Anastrozole in the drug label.

Pharmacology

There is limited information regarding Anastrozole Pharmacology in the drug label.

Mechanism of Action

Structure

This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Anastrozole in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Anastrozole in the drug label.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Anastrozole in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Anastrozole in the drug label.

How Supplied

Storage

There is limited information regarding Anastrozole Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Patient Counseling Information of Anastrozole in the drug label.

Precautions with Alcohol

  • Alcohol-Anastrozole interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

Look-Alike Drug Names

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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